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2008 Grants - Marr
Investigation of the Role of MMEL in Protection from Alzheimer's Disease
Robert A. Marr, Ph.D.
Rosalind Franklin University of Medicine and Science
North Chicago, Illinois
2008 New Investigator Research Grant
Amyloid plaques, a characteristic feature of Alzheimer pathology, are constructed of large aggregates of beta-amyloid, a protein fragment found in the brain. It has been suggested that increasing the ability of the brain to clear beta-amyloid may be a useful approach to slowing or halting progression of the disease.
One enzyme that degrades beta-amyloid in the human brain has already been characterized. A second beta-amyloid-degrading enzyme has been described in mice. Blocking the expression of this gene in mice causes increases in beta-amyloid levels in the brain. Robert A. Marr, Ph.D., and colleagues are characterizing the human version of this second enzyme, named membrane metallo-endopeptidase-like protein (MMEL). They have already shown that one version of MMEL (MMELb) is able to degrade beta-amyloid.
Dr. Marr and colleagues plan to extend their studies of MMEL to understand its role in Alzheimer's disease. They will quantify the expression of different versions of MMEL in human brain samples from healthy individuals and from individuals with Alzheimer's disease. The researchers will also genetically engineer mice to express high levels of MMELb to determine if such treatment reduces accumulation of beta-amyloid and preserves cognitive function. These studies may improve our understanding of how beta-amyloid is degraded, and they may suggest opportunities for the development of new treatment strategies for Alzheimer's disease.